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PDBsum entry 1at0

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protein links
Signaling protein PDB id
1at0
Jmol
Contents
Protein chain
145 a.a. *
Waters ×378
* Residue conservation analysis
PDB id:
1at0
Name: Signaling protein
Title: 17-kda fragment of hedgehog c-terminal autoprocessing domain
Structure: 17-hedgehog. Chain: a. Fragment: 17-kda fragment of c-terminal domain. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Cell_line: b834. Expressed in: escherichia coli.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.218     R-free:   0.275
Authors: T.M.T.Hall,J.A.Porter,K.E.Young,E.V.Koonin,P.A.Beachy, D.J.Leahy
Key ref:
T.M.Hall et al. (1997). Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins. Cell, 91, 85-97. PubMed id: 9335337 DOI: 10.1016/S0092-8674(01)80011-8
Date:
15-Aug-97     Release date:   12-Nov-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q02936  (HH_DROME) -  Protein hedgehog
Seq:
Struc:
471 a.a.
145 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     cell communication   4 terms 
  Biochemical function     peptidase activity     1 term  

 

 
DOI no: 10.1016/S0092-8674(01)80011-8 Cell 91:85-97 (1997)
PubMed id: 9335337  
 
 
Crystal structure of a Hedgehog autoprocessing domain: homology between Hedgehog and self-splicing proteins.
T.M.Hall, J.A.Porter, K.E.Young, E.V.Koonin, P.A.Beachy, D.J.Leahy.
 
  ABSTRACT  
 
The approximately 25 kDa carboxy-terminal domain of Drosophila Hedgehog protein (Hh-C) possesses an autoprocessing activity that results in an intramolecular cleavage of full-length Hedgehog protein and covalent attachment of a cholesterol moiety to the newly generated amino-terminal fragment. We have identified a 17 kDa fragment of Hh-C (Hh-C17) active in the initiation of autoprocessing and report here its crystal structure. The Hh-C17 structure comprises two homologous subdomains that appear to have arisen from tandem duplication of a primordial gene. Residues in the Hh-C17 active site have been identified, and their role in Hedgehog autoprocessing probed by site-directed mutagenesis. Aspects of sequence, structure, and reaction mechanism are conserved between Hh-C17 and the self-splicing regions of inteins, permitting reconstruction of a plausible evolutionary history of Hh-C and the inteins.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Structure of Hh-C[17](A) Ribbon diagram of Hh-C[17]. The amino (N) and carboxyl (C) termini are labeled. This panel was prepared with MOLSCRIPT ([25]).(B) Topology diagram of Hh-C[17]. Residues in β strands are in boxes with amino acid type and number indicated. Residues in turns of 3[10] helix are in ovals with amino acid type and number indicated. Other residues in the structure are in boxes with amino acid number indicated. Hydrogen bonds between β strands are indicated with arrows. A pseudo 2-fold axis of symmetry is indicated with a diamond. This panel was prepared using the output of the program PROMOTIF ([20]).
Figure 7.
Figure 7. Insertions in the PI-SceI Intein Relative to Hh-C[17]Stereo ribbon diagram of Hh-C[17], indicating where the endonuclease domain and additional DNA recognition region of PI-SceI are inserted is shown. The loop where the endonuclease domain is inserted is colored red, and the loop where the additional DNA recognition region (“the arm of the self-splicing domain”[10]) is inserted is colored blue. The orientation of Hh-C[17] in this view is the same as the orientation of the PI-SceI intein in Figure 2 of [10]. This panel was prepared with MOLSCRIPT ( [25]).
 
  The above figures are reprinted by permission from Cell Press: Cell (1997, 91, 85-97) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21221452 W.P.Heal, B.Jovanovic, S.Bessin, M.H.Wright, A.I.Magee, and E.W.Tate (2011).
Bioorthogonal chemical tagging of protein cholesterylation in living cells.
  Chem Commun (Camb), 47, 4081-4083.  
21357747 X.Chen, H.Tukachinsky, C.H.Huang, C.Jao, Y.R.Chu, H.Y.Tang, B.Mueller, S.Schulman, T.A.Rapoport, and A.Salic (2011).
Processing and turnover of the Hedgehog protein in the endoplasmic reticulum.
  J Cell Biol, 192, 825-838.  
19940146 K.Tori, B.Dassa, M.A.Johnson, M.W.Southworth, L.E.Brace, Y.Ishino, S.Pietrokovski, and F.B.Perler (2010).
Splicing of the mycobacteriophage Bethlehem DnaB intein: identification of a new mechanistic class of inteins that contain an obligate block F nucleophile.
  J Biol Chem, 285, 2515-2526.  
20449740 S.Elleuche, and S.Pöggeler (2010).
Inteins, valuable genetic elements in molecular biology and biotechnology.
  Appl Microbiol Biotechnol, 87, 479-489.  
19603532 E.Roessler, K.B.El-Jaick, C.Dubourg, J.I.Vélez, B.D.Solomon, D.E.Pineda-Alvarez, F.Lacbawan, N.Zhou, M.Ouspenskaia, A.Paulussen, H.J.Smeets, U.Hehr, C.Bendavid, S.Bale, S.Odent, V.David, and M.Muenke (2009).
The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis.
  Hum Mutat, 30, E921-E935.  
19213802 E.V.Koonin, and C.Darwin (2009).
Darwinian evolution in the light of genomics.
  Nucleic Acids Res, 37, 1011-1034.  
19564910 G.Hausmann, C.von Mering, and K.Basler (2009).
The hedgehog signaling pathway: where did it come from?
  PLoS Biol, 7, e1000146.  
19708049 H.D.Mootz (2009).
Split inteins as versatile tools for protein semisynthesis.
  Chembiochem, 10, 2579-2589.  
19153786 M.Dori-Bachash, B.Dassa, O.Peleg, S.A.Pineiro, E.Jurkevitch, and S.Pietrokovski (2009).
Bacterial intein-like domains of predatory bacteria: a new domain type characterized in Bdellovibrio bacteriovorus.
  Funct Integr Genomics, 9, 153-166.  
19666710 R.Raghavan, and M.F.Minnick (2009).
Group I introns and inteins: disparate origins but convergent parasitic strategies.
  J Bacteriol, 191, 6193-6202.  
18334026 T.R.Bürglin (2008).
Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins in ancestral eukaryotes and discovery of a novel Hint motif.
  BMC Genomics, 9, 127.  
19040769 T.R.Bürglin (2008).
The Hedgehog protein family.
  Genome Biol, 9, 241.  
17586768 M.A.Johnson, M.W.Southworth, T.Herrmann, L.Brace, F.B.Perler, and K.Wüthrich (2007).
NMR structure of a KlbA intein precursor from Methanococcus jannaschii.
  Protein Sci, 16, 1316-1328.
PDB codes: 2jmz 2jnq
17254599 P.Van Roey, B.Pereira, Z.Li, K.Hiraga, M.Belfort, and V.Derbyshire (2007).
Crystallographic and mutational studies of Mycobacterium tuberculosis recA mini-inteins suggest a pivotal role for a highly conserved aspartate residue.
  J Mol Biol, 367, 162-173.
PDB codes: 2imz 2in0 2in8 2in9
16615205 E.A.Snell, N.M.Brooke, W.R.Taylor, D.Casane, H.Philippe, and P.W.Holland (2006).
An unusual choanoflagellate protein released by Hedgehog autocatalytic processing.
  Proc Biol Sci, 273, 401-407.  
16493661 H.Matsumura, H.Takahashi, T.Inoue, T.Yamamoto, H.Hashimoto, M.Nishioka, S.Fujiwara, M.Takagi, T.Imanaka, and Y.Kai (2006).
Crystal structure of intein homing endonuclease II encoded in DNA polymerase gene from hyperthermophilic archaeon Thermococcus kodakaraensis strain KOD1.
  Proteins, 63, 711-715.
PDB codes: 2cw7 2cw8
15987679 F.Levitin, O.Stern, M.Weiss, C.Gil-Henn, R.Ziv, Z.Prokocimer, N.I.Smorodinsky, D.B.Rubinstein, and D.H.Wreschner (2005).
The MUC1 SEA module is a self-cleaving domain.
  J Biol Chem, 280, 33374-33386.  
15803137 J.E.Hooper, and M.P.Scott (2005).
Communicating with Hedgehogs.
  Nat Rev Mol Cell Biol, 6, 306-317.  
16000767 K.Nagasaki, Y.Shirai, Y.Tomaru, K.Nishida, and S.Pietrokovski (2005).
Algal viruses with distinct intraspecies host specificities include identical intein elements.
  Appl Environ Microbiol, 71, 3599-3607.  
15020462 A.Bakhrat, M.S.Jurica, B.L.Stoddard, and D.Raveh (2004).
Homology modeling and mutational analysis of Ho endonuclease of yeast.
  Genetics, 166, 721-728.  
15087498 A.Romanelli, A.Shekhtman, D.Cowburn, and T.W.Muir (2004).
Semisynthesis of a segmental isotopically labeled protein splicing precursor: NMR evidence for an unusual peptide bond at the N-extein-intein junction.
  Proc Natl Acad Sci U S A, 101, 6397-6402.  
15150275 B.Dassa, H.Haviv, G.Amitai, and S.Pietrokovski (2004).
Protein splicing and auto-cleavage of bacterial intein-like domains lacking a C'-flanking nucleophilic residue.
  J Biol Chem, 279, 32001-32007.  
15292211 E.Traiffort, C.Dubourg, H.Faure, D.Rognan, S.Odent, M.R.Durou, V.David, and M.Ruat (2004).
Functional characterization of sonic hedgehog mutations associated with holoprosencephaly.
  J Biol Chem, 279, 42889-42897.  
15189162 R.K.Mann, and P.A.Beachy (2004).
Novel lipid modifications of secreted protein signals.
  Annu Rev Biochem, 73, 891-923.  
14760742 S.Steuer, V.Pingoud, A.Pingoud, and W.Wende (2004).
Chimeras of the homing endonuclease PI-SceI and the homologous Candida tropicalis intein: a study to explore the possibility of exchanging DNA-binding modules to obtain highly specific endonucleases with altered specificity.
  Chembiochem, 5, 206-213.  
15342554 T.J.Templeton, L.M.Iyer, V.Anantharaman, S.Enomoto, J.E.Abrahante, G.M.Subramanian, S.L.Hoffman, M.S.Abrahamsen, and L.Aravind (2004).
Comparative analysis of apicomplexa and genomic diversity in eukaryotes.
  Genome Res, 14, 1686-1695.  
15194682 W.Sun, J.Yang, and X.Q.Liu (2004).
Synthetic two-piece and three-piece split inteins for protein trans-splicing.
  J Biol Chem, 279, 35281-35286.  
14633979 F.Schmitzberger, M.L.Kilkenny, C.M.Lobley, M.E.Webb, M.Vinkovic, D.Matak-Vinkovic, M.Witty, D.Y.Chirgadze, A.G.Smith, C.Abell, and T.L.Blundell (2003).
Structural constraints on protein self-processing in L-aspartate-alpha-decarboxylase.
  EMBO J, 22, 6193-6204.
PDB codes: 1ppy 1pqe 1pqf 1pqh 1pt0 1pt1 1pyq 1pyu
12492854 G.Amitai, O.Belenkiy, B.Dassa, A.Shainskaya, and S.Pietrokovski (2003).
Distribution and function of new bacterial intein-like protein domains.
  Mol Microbiol, 47, 61-73.  
12914579 P.E.Jira, H.R.Waterham, R.J.Wanders, J.A.Smeitink, R.C.Sengers, and R.A.Wevers (2003).
Smith-Lemli-Opitz syndrome and the DHCR7 gene.
  Ann Hum Genet, 67, 269-280.  
12878593 Y.Ding, M.Q.Xu, I.Ghosh, X.Chen, S.Ferrandon, G.Lesage, and Z.Rao (2003).
Crystal structure of a mini-intein reveals a conserved catalytic module involved in side chain cyclization of asparagine during protein splicing.
  J Biol Chem, 278, 39133-39142.
PDB code: 1mi8
11880638 A.L.Simon, E.A.Stone, and A.Sidow (2002).
Inference of functional regions in proteins by quantification of evolutionary constraints.
  Proc Natl Acad Sci U S A, 99, 2912-2917.  
12219083 C.M.Moure, F.S.Gimble, and F.A.Quiocho (2002).
Crystal structure of the intein homing endonuclease PI-SceI bound to its recognition sequence.
  Nat Struct Biol, 9, 764-770.
PDB codes: 1lws 1lwt
12235380 E.Werner, W.Wende, A.Pingoud, and U.Heinemann (2002).
High resolution crystal structure of domain I of the Saccharomyces cerevisiae homing endonuclease PI-SceI.
  Nucleic Acids Res, 30, 3962-3971.
PDB code: 1gpp
  12208857 J.Jeong, and A.P.McMahon (2002).
Cholesterol modification of Hedgehog family proteins.
  J Clin Invest, 110, 591-596.  
12142479 J.P.Gogarten, A.G.Senejani, O.Zhaxybayeva, L.Olendzenski, and E.Hilario (2002).
Inteins: structure, function, and evolution.
  Annu Rev Microbiol, 56, 263-287.  
11517925 A.J.Barrett, and N.D.Rawlings (2001).
Evolutionary lines of cysteine peptidases.
  Biol Chem, 382, 727-733.  
11576188 E.Traiffort, K.L.Moya, H.Faure, R.Hässig, and M.Ruat (2001).
High expression and anterograde axonal transport of aminoterminal sonic hedgehog in the adult hamster brain.
  Eur J Neurosci, 14, 839-850.  
11600710 F.S.Gimble (2001).
Degeneration of a homing endonuclease and its target sequence in a wild yeast strain.
  Nucleic Acids Res, 29, 4215-4223.  
10828056 B.W.Poland, M.Q.Xu, and F.A.Quiocho (2000).
Structural insights into the protein splicing mechanism of PI-SceI.
  J Biol Chem, 275, 16408-16413.
PDB code: 1ef0
10684923 C.Saguez, G.Lecellier, and F.Koll (2000).
Intronic GIY-YIG endonuclease gene in the mitochondrial genome of Podospora curvicolla: evidence for mobility.
  Nucleic Acids Res, 28, 1299-1306.  
10644733 D.Hu, M.Crist, X.Duan, F.A.Quiocho, and F.S.Gimble (2000).
Probing the structure of the PI-SceI-DNA complex by affinity cleavage and affinity photocross-linking.
  J Biol Chem, 275, 2705-2712.
PDB code: 1dfa
10892642 E.V.Koonin, L.Aravind, and A.S.Kondrashov (2000).
The impact of comparative genomics on our understanding of evolution.
  Cell, 101, 573-576.  
10592269 F.B.Perler (2000).
InBase, the Intein Database.
  Nucleic Acids Res, 28, 344-345.  
10966466 H.Paulus (2000).
Protein splicing and related forms of protein autoprocessing.
  Annu Rev Biochem, 69, 447-496.  
10798399 J.Beneken, J.C.Tu, B.Xiao, M.Nuriya, J.P.Yuan, P.F.Worley, and D.J.Leahy (2000).
Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition.
  Neuron, 26, 143-154.
PDB codes: 1ddv 1ddw
10870957 J.G.Henikoff, S.Pietrokovski, C.M.McCallum, and S.Henikoff (2000).
Blocks-based methods for detecting protein homology.
  Electrophoresis, 21, 1700-1706.  
10990465 M.W.Southworth, J.Benner, and F.B.Perler (2000).
An alternative protein splicing mechanism for inteins lacking an N-terminal nucleophile.
  EMBO J, 19, 5019-5026.  
  10921907 P.E.Kuwabara, M.H.Lee, T.Schedl, and G.S.Jefferis (2000).
A C. elegans patched gene, ptc-1, functions in germ-line cytokinesis.
  Genes Dev, 14, 1933-1944.  
11111088 R.K.Mann, and P.A.Beachy (2000).
Cholesterol modification of proteins.
  Biochim Biophys Acta, 1529, 188-202.  
11092822 X.Q.Liu (2000).
Protein-splicing intein: Genetic mobility, origin, and evolution.
  Annu Rev Genet, 34, 61-76.  
10366843 F.B.Perler (1999).
A natural example of protein trans-splicing.
  Trends Biochem Sci, 24, 209-211.  
10500183 J.S.Rosenblum, and G.Blobel (1999).
Autoproteolysis in nucleoporin biogenesis.
  Proc Natl Acad Sci U S A, 96, 11370-11375.  
10607613 L.Aravind, and G.Subramanian (1999).
Origin of multicellular eukaryotes - insights from proteome comparisons.
  Curr Opin Genet Dev, 9, 688-694.  
10490104 Q.Xu, D.Buckley, C.Guan, and H.C.Guo (1999).
Structural insights into the mechanism of intramolecular proteolysis.
  Cell, 98, 651-661.
PDB codes: 9gaa 9gac 9gaf
9512547 A.E.Gorbalenya (1998).
Non-canonical inteins.
  Nucleic Acids Res, 26, 1741-1748.  
9437416 B.L.Stoddard, and S.Pietrokovski (1998).
Breaking up is hard to do.
  Nat Struct Biol, 5, 3-5.  
9546209 F.B.Perler (1998).
Breaking up is easy with esters.
  Nat Struct Biol, 5, 249-252.  
9489693 F.B.Perler (1998).
Protein splicing of inteins and hedgehog autoproteolysis: structure, function, and evolution.
  Cell, 92, 1-4.  
9818144 F.S.Gimble (1998).
Putting protein splicing to work.
  Chem Biol, 5, R251-R256.  
9685368 H.C.Guo, Q.Xu, D.Buckley, and C.Guan (1998).
Crystal structures of Flavobacterium glycosylasparaginase. An N-terminal nucleophile hydrolase activated by intramolecular proteolysis.
  J Biol Chem, 273, 20205-20212.
PDB codes: 2gac 2gaw
9520402 K.V.Mills, B.M.Lew, S.Jiang, and H.Paulus (1998).
Protein splicing in trans by purified N- and C-terminal fragments of the Mycobacterium tuberculosis RecA intein.
  Proc Natl Acad Sci U S A, 95, 3543-3548.  
9883719 L.V.Goodrich, and M.P.Scott (1998).
Hedgehog and patched in neural development and disease.
  Neuron, 21, 1243-1257.  
9463370 M.W.Southworth, E.Adam, D.Panne, R.Byer, R.Kautz, and F.B.Perler (1998).
Control of protein splicing by intein fragment reassembly.
  EMBO J, 17, 918-926.  
9666333 R.B.Russell, and C.P.Ponting (1998).
Protein fold irregularities that hinder sequence analysis.
  Curr Opin Struct Biol, 8, 364-371.  
9729722 R.L.Johnson, and M.P.Scott (1998).
New players and puzzles in the Hedgehog signaling pathway.
  Curr Opin Genet Dev, 8, 450-456.  
9540409 R.V.Farese, and J.Herz (1998).
Cholesterol metabolism and embryogenesis.
  Trends Genet, 14, 115-120.  
9851918 S.A.Chervitz, L.Aravind, G.Sherlock, C.A.Ball, E.V.Koonin, S.S.Dwight, M.A.Harris, K.Dolinski, S.Mohr, T.Smith, S.Weng, J.M.Cherry, and D.Botstein (1998).
Comparison of the complete protein sets of worm and yeast: orthology and divergence.
  Science, 282, 2022-2028.  
9437427 T.Klabunde, S.Sharma, A.Telenti, W.R.Jacobs, and J.C.Sacchettini (1998).
Crystal structure of GyrA intein from Mycobacterium xenopi reveals structural basis of protein splicing.
  Nat Struct Biol, 5, 31-36.
PDB code: 1am2
9518476 W.Grindl, W.Wende, V.Pingoud, and A.Pingoud (1998).
The protein splicing domain of the homing endonuclease PI-sceI is responsible for specific DNA binding.
  Nucleic Acids Res, 26, 1857-1862.  
9468518 Z.He, M.Crist, H.Yen, X.Duan, F.A.Quiocho, and F.S.Gimble (1998).
Amino acid residues in both the protein splicing and endonuclease domains of the PI-SceI intein mediate DNA binding.
  J Biol Chem, 273, 4607-4615.  
9358175 J.Z.Dalgaard, A.J.Klar, M.J.Moser, W.R.Holley, A.Chatterjee, and I.S.Mian (1997).
Statistical modeling and analysis of the LAGLIDADG family of site-specific endonucleases and identification of an intein that encodes a site-specific endonuclease of the HNH family.
  Nucleic Acids Res, 25, 4626-4638.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.